We will use the awake rat to investigate whether ventilation follows the changes in acid-base balance, central respiratory drive, and lung mechanics during prolonged hypercapnia. Awake rats will be continuously exposed to 4% CO2 for up to three weeks. Minute ventilation, lung mechanics, respiratory drive and acid-base parameters will be measured during the last 10 minutes of a certain period of hypercapnia. We will use these data to analyze factors contributing to the change in ventilation during different periods of CO2 inhalation. In order to look into the effect of hypercapnia-hypoxia interaction on ventilation during moderate long time exposure, we plan to do above measurements in the awake rat breathing 4% CO2 - 10% O2. To determine the site of action of CO2, we will perform studies in awake rats with denervated peripheral chemoreceptors, i.e., with cut carotid sinus nerves, during prolonged hypercapnic exposure.